PXD011330-1

PXD011330 is an original dataset announced via ProteomeXchange.

Title	Assessing Technical and Biological Variation in SWATH-MS -based Proteomics: A case study in Chronic Lymphocytic Leukaemia
Description	Chronic lymphocytic leukaemia (CLL) is renowned for its variable clinical course and response to therapy, suggesting a role for precision medicine. However, the molecular basis of CLL variability remains incompletely understood. Recent developments in data independent acquisition (DIA) -MS technologies, such as SWATH (Sequential Windowed Acquisition of all THeoretical fragments), provide an opportunity to study the pathophysiology of CLL at the proteome level. This report describes the sample replication and data handling requirements for SWATH-MS analysis of clinical samples. A CLL-specific spectral library compromising over 1,500,000 spectra with digital information for over 150,000 peptides has been generated to enable the quantification of up to 7736 proteins. To assess the reproducibility of the assay, SWATH-MS analysis was performed on 6 cryopreserved CLL patient samples, incorporating biological (IGHV mutational status), sample preparation and MS technical replicates. Quantitative information was obtained for 5169 proteins (<1% FDR) across 54 SWATH-MS acquisitions. These analyses showed that SWATH-MS is a highly reproducible technique. However, replicate sample preparations on different days was identified as the main source of variation. To overcome the effect of variation between sample preparation batches, different computational approaches for batch correction were tested. All approaches successfully removed technical variability whilst retaining proteomic differences between clinical subgroups. Functional enrichment analysis of proteins associated to IGHV mutational status highlighted the importance of metabolic remodelling in the biology of CLL and overlapped significantly with previous studies based on gene expression profiling. Finally, an approach to perform statistical power analysis in proteomics studies was developed. This approach could be used to drive the design of future CLL SWATH-MS studies. These fundamental requirements for DIA approaches should be widely applicable to other clinical proteomics studies.
HostingRepository	PRIDE
AnnounceDate	2021-02-05
AnnouncementXML	Submission_2021-02-05_06:47:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gina Eagle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-10 05:38:39	ID requested
⏵ 1	2021-02-05 06:47:34	announced
2	2023-11-14 08:49:48	announced	2023-11-14: Updated project metadata.

10.1038/S41598-021-82609-2;

curator keyword: Biomedical

submitter keyword: CLL, SWATH, Leukaemia

Dr Rosalind Jenkins
contact affiliation	MRC Centre for Drug Safety Science, Dept. Molecular & Clinical Pharmacology, Institute for Translational Medicine, University of Liverpool, UK.
contact email	R.Jenkins@liv.ac.uk
lab head
Gina Eagle
contact affiliation	University of Liverpool
contact email	gleagle@liverpool.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011330
     1. Label: PRIDE project
     2. Name: Assessing Technical and Biological Variation in SWATH-MS -based Proteomics: A case study in Chronic Lymphocytic Leukaemia